tbuckley/cabot-search huggingface dataset:
PB2341: MIDAZOLAM AND LOCAL ANAESTHESIA CO-ADMINISTRATION GIVES BETTER PAIN CONTROL DURING THE BONE MARROW ASPIRATION AND BIOPSY PROCEDURE
Authors: Z. C. Chapanduka
Journal: HemaSphere (2022)

Background: During the bone marrow aspiration and biopsy (BMAB) procedure, patients report pain of varying intensity ranging from complete absence of pain to severe pain. There is limited literature on the patient and procedure related factors associated with the pain. Furthermore, evidence-based guidelines on the best method of pain management during BMAB are lacking. The use of local anaesthesia(LA) only is still widespread although it does not abolish the pain of BMAB. Conscious sedation, other pharmacological agents and non-pharmacological interventions are used to a variable extent. Midazolam is the most commonly used benzodiazepine for conscious sedation and may be used in conjunction with local anaesthesia, other systemic pharmacological agents or as a single agent. Our centre introduced universal midazolam sedation unless there is a contraindication to its use, 4 years ago. Aims: To assess the impact of the universal use of intravenous midazolam premedication for the BMAB procedure compared to the use of local anaesthesia only and to determine the patient- and procedure-related factors associated with the patient-reported pain. Methods: A retrospective cross-sectional study was performed on adult patients who had a BMAB in a day procedure operating theatre over the period from 1st July 2018 to 30th March 2019. Patient demographics, the body mass index (BMI), indications, diagnosis, the number of times the patient had the BMAB procedure and the experience of the operator were documented. A numerical rating scale pain assessment tool and questionnaire were used in interviews conducted by the principal investigator. Further data were extracted from the National Health Laboratory Service laboratory information system, patients’ hospital files and the operating theatre records. Results: A total of 182 BMAB procedures were included in the study; 155 procedures performed with midazolam premedication and 27 performed using local anaesthesia only. Pain was reported in all procedures performed under local anaesthesia and only in 29.1% of procedures performed with midazolam administration. Our study showed no influence of age, sex, race, level of educations, indication, diagnosis, experience of the operator on pain. Patients who had previous BMAB experienced less pain. Midazolam dose showed negative correlation with pain. Summary/Conclusion: Local anaesthesia only is not enough to abolish pain of BMAB. Midazolam conscious sedation used with local anaesthesia consistently reduces the reported pain to acceptable levels. Patients with previous experience of BMAB under midazolam premedication reported less pain. The universal use of midazolam conscious sedation for BMAB under carefully controlled circumstances is strongly recommended.
Association of Receipt of the Fourth BNT162b2 Dose With Omicron Infection and COVID-19 Hospitalizations Among Residents of Long-term Care Facilities
Authors: Khitam Muhsen, Nimrod Maimon, Amiel Yaron Mizrahi, Boris Boltyansky, Omri Bodenheimer, Zafrira Hillel Diamant, Lea Gaon, Dani Cohen, Ron Dagan
Journal: JAMA Internal Medicine (2022)

The administration of a fourth BNT162b2 COVID-19 vaccine dose was approved in Israel in December 2021 for individuals 60 years or older who were vaccinated with a third dose 4 months previously or earlier to control the substantial surge of the SARS-CoV-2 Omicron variant. Nonetheless, the association between receipt of the fourth dose and protection against infection remains elusive.To determine the association of the fourth BNT162b2 dose with protection against SARS-CoV-2-related infections, hospitalizations, and deaths during the Omicron surge in long-term care facility (LTCF) residents.This prospective cohort study was conducted in Israel between January 10 and March 31, 2022 and included LTCF residents 60 years or older.Vaccination with the fourth dose of BNT162b2 vs 3 doses that were administered 4 months previously or earlier.Cumulative incidences of SARS-CoV-2 infections, hospitalizations, and deaths during the Omicron surge. The follow-up was initiated more than 7 days after receipt of the fourth dose, which was matched to the follow-up initiation date of those who had received 3 doses of vaccine in each facility. We obtained hazard ratios and 95% confidence intervals from multivariable Cox regression models.The data of 43 775 residents (mean [SD] age, 80.1 [9.4] years; 29 679 women [67.8%]) were analyzed, of whom 24 088 (55.0%) and 19 687 (45.0%) received the fourth and third dose (4 months previously or earlier), respectively. The median follow-up time was 73 days (4-dose group: IQR, 6 days; 3-dose group: IQR, 56 days). More than 7 days postvaccination with the fourth dose, SARS-CoV-2 infection was detected among 4058 fourth-dose vs 4370 third-dose recipients (cumulative incidence, 17.6% vs 24.9%). The corresponding incidences of hospitalizations for mild-to-moderate COVID-19, severe illness, and mortality were 0.9% and 2.8%, 0.5% and 1.5%, and 0.2% and 0.5%, respectively. The adjusted protections were 34% (95% CI, 30%-37%), 64% (95% CI, 56%-71%), and 67% (95% CI, 57%-75%) against overall infection, hospitalizations for mild-to-moderate illness, and severe illness, respectively, and 72% (95% CI, 57%-83%) against related deaths.The results of this cohort study suggest that receipt of a fourth BNT162b2 dose conferred high protection against COVID-19 hospitalizations and deaths among LTCF residents during a substantial Omicron variant surge, but protection was modest against infection. These findings are relevant to the control of COVID-19 pandemic globally, especially among the population of LTCFs.
P1601: THE ASSESSMENT OF PREDICTIVE ROLE OF PROTEIN C AND S FOR CRITICAL FORM OF COVID-19
Authors: V. Popov, M. Andreescu, O. Patrinoiu, M. Popescu, M. Omer, F. Mihai, G. Ofiteru, C. Despan, O. Constantin, C. Pirvu, A. Grigorie, A. Rus, M. D. Badoiu Niculae, A. Badea, L. Iliescu
Journal: HemaSphere (2022)

Background: COVID-19 is characterized by an excessive immune response in the host “cytokine storm”, followed by extensive tissue damage, dysfunctional coagulation and thrombotic complication. The presence of thrombosis worsens the evolution of COVID-19 caused by refractory hypoxemia, respiratory failure, disseminated intravascular coagulation or death. Aims: The main objective of our study was to evaluate the presence of any correlation between anticoagulants (protein S, protein C, antithrombin III) and clinical/laboratory features of critical forms of COVID 19 admitted in intensive care unit (ICU). Methods: This observational study (retrospective and prospective) included 268 COVID-19 patients hospitalised Colentina Clinical Hospital Bucharest 2020-2021 and confirmed by real-time reverse transcriptase polymerase chain reaction (PCR) test. The study group was divided into two groups depending on the type of medical care required - medical care (non-ICU group) and intensive care (ICU group). Results: The level of protein C and S is lower in COVID-19 patients with thrombosis compared with patients without thrombotic complication (median value: protein S: 43.5 (8-102) vs. 56 (18-144), p=0.05; protein C: 71 (15-169) vs. 95 (16-200), p=0.02). Critical forms of COVID 19 is associated with low level of protein S (ICU: 48 (8-122) vs. non-ICU: 63 (18-144), p=0.001); protein C (ICU: 82 (15-170) vs non-ICU: 96.5 (55-200), p=0.02). There are significant correlation between low level of protein S and duration of hospitalization in ICU department, rho=-0.367 (-0.541- -0.163) p=0.0007. In survival analyses only protein C level was predictive for unfavourable evolution, Wald 8.55, p=0.003. This parameter associated with high level of feritine and IL-6, are very important in evaluation of COVID-19 patients with unfavourable evolution. Prolonged positivity is associated with low level of protein S, rho -0.517 (-0.75- -0.171), p=0.006. Summary/Conclusion: Evaluation of level of protein S and C in COVID-19 patient is very important at the admission moment in ICU. Low level of protein S is associated with prolonged positivity, unfavourable evolution and hiperinflamation. It also associated with thrombotic complication and cytokine storm (IL-6), all these modification contributed in high rate of ICU admission
PB2217: SICKLE CELL DISEASE IS A RISK FACTOR FOR THE PROGRESSION AND PROGNOSIS OF COVID-19
Authors: V. Goyal, A. Singh, Y. Memon, N. Thakre, P. Sahu, R. Goyal
Journal: HemaSphere (2022)

Background: Since December 2019, COVID-19 has aroused global attention. Studies show the link between many comorbid condition and severe outcome incoronavirus disease 2019 (COVID-19). There are limited number of studies regarding the association between sickle cell disease and COVID-19 outcomes. Aims: To figure out whether sickle cell disease is a risk factor influencing the progression and prognosis of 2019 novel coronavirus disease (COVID-19). Methods: A total of 152 consecutive patients confirmed with COVID-19 were studied. Demographic data, medical history, symptoms and signs, laboratory findings, chest computed tomography (CT) as well the treatment measures were collected and analysed. Results: We found that COVID-19 patients without other comorbidities but with sickle cell disease (n = 18) were at higher risk of severe pneumonia, release of tissue injury-related enzymes, excessive uncontrolled inflammation responses and hypercoagulable state associated with sickle cell pathology. Furthermore, serum levels of inflammation-related biomarkers such as IL-6, C-reactive protein, serum ferritin and coagulation index, D-dimer, were significantly higher (P < .01) in sickle cell patients compared with those without, suggesting that patients with sickle cell disease are more susceptible to an inflammatory storm eventually leading to rapid deterioration of COVID-19.The frequency of death (sickle: 23.9% vs. nonsickle: 13.8%), ICU admission (sickle: 27.8% vs. nonsickle:14.71%), and ventilator requirement (sickle: 35.93% vs. nonsickle: 20.63%) were significantly higher in sickle patients than in nonsickle patients (P < 0.001). Image:Summary/Conclusion: Our data support the notion that sickle cell disease should be considered as a risk factor for a rapid progression and bad prognosis of COVID-19. More intensive attention should be paid to sickle cell disease patients having COVID-19 infection.
Abstract LB198: Cellular selectivity of STING stimulation determines priming of anti-tumor T cell responses
Authors: Bakhos Jneid, Aurore Bochnakian, Fabien Delisle, Emeline Djacoto, Jordan Denizeau, Christine Sedlik, Frédéric Fiore, Robert Kramer, Ian Walters, Sylvain Carlioz, Bernard Malissen, Eliane Piaggio, Nicolas Manel
Journal: Cancer Research (2022)

Abstract T cells that recognize tumor antigens are crucial for anti-tumor immune responses. Induction of anti-tumor T cells in immunogenic tumors depends on STING, the intracellular innate immune receptor for cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) and related cyclic dinucleotides (CDN). However, the optimal way to leverage STING activation in non-immunogenic tumors is still unclear. Here, we show that cGAMP delivery by intra-tumoral injection of virus-like particles (cGAMP-VLP) leads to differentiation of tumor-specific T cells, decrease in tumor regulatory T cells (Tregs) and anti-tumoral responses that synergize with PD1 blockade. By contrast, intra-tumoral injection of synthetic CDN leads to tumor necrosis and systemic T cell activation but no differentiation of tumor-specific T cells, and a demise of immune cells in injected tumors. Analyses of cytokine responses and genetic models revealed that cGAMP-VLP preferentially targets STING in dendritic cells at a 1000-fold less dose than synthetic CDN. Sub-cutaneous administration of cGAMP-VLP showed synergy when combined with a tumor Treg-depleting antibody to elicit systemic tumor-specific T cells, leading to complete and lasting tumor eradication. These findings show that cell targeting of STING stimulation shapes the anti-tumor T cell response and reveal a therapeutic strategy with T cell modulators, which may address the current limitations of STING-based approaches in patients. Citation Format: Bakhos Jneid, Aurore Bochnakian, Fabien Delisle, Emeline Djacoto, Jordan Denizeau, Christine Sedlik, Frédéric Fiore, Robert Kramer, Ian Walters, Sylvain Carlioz, Bernard Malissen, Eliane Piaggio, Nicolas Manel. Cellular selectivity of STING stimulation determines priming of anti-tumor T cell responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB198.
Clinical study of urethroplasty combined free grafting of internal preputial lamina with onlay local pedicled flap
Authors: G. Wu, X. Zou, Y. Wu, Z. Zhang, Y. Yuan, G. Zhang, R. Xiao, X. Wang, H. Xu, F. Liu, Y. Liao, W. Xia, R. Huang
Journal: European Urology (2022)
P1411: DUAL EPIGENETIC AND GENETIC EDITING OF PRIMARY HUMAN HAEMATOPOIETIC STEM AND PROGENITOR CELLS
Authors: E. Saunderson, H. Encabo, K. Rouault-Pierre, M. Piganeau, D. Bonnet, J. Gribben, G. Ficz
Journal: HemaSphere (2022)

Background: The epigenome is perturbed in haematological malignancies including localized DNA hypermethylation at the gene promoter CpG islands. The impact of these hypermethylation events on normal cell function is unknown due to a lack of appropriate methods to edit the epigenome in human primary haematopoietic stem and progenitor cells (HSPCs). For example, INK4b (p15) promoter hypermethylation is frequently found in acute myeloid leukaemia (AML), but whether this can contribute to disease causation is not known. It is also unknown whether sporadic age-associated DNA methylation is maintained during HPSC differentiation. Aims: To address this, we edited the epigenome of human HSPCs using a modified form of CRISPR/dCas9 that targets DNA methylation rather than mutations in cells. Our aim was to target DNA methylation to key cell cycle regulators, p15 (INK4b) and p14 (ARF), test maintenance of DNA methylation as cells differentiate in vitro and in vivo, and assess the biological impact. We also aimed to multiplex CRISPR/Cas9 editing to generate a TET2 mutation and p15 hypermethylation in the same HSPC. Methods: We nucleofected human HSPCs from umbilical cord blood with an in vitro transcribed form of CRISPR/dCas9 containing a portion of the DNA methyltransferase enzyme 3A (DNMT3A) and DNMT3L, along with guide RNAs (gRNAs) to target the p15 and p14 promoters. In some experiments we also nucleofected HSPCs using the nuclease form of Cas9 with a gRNA targeting TET2. To assess the level of editing and the biological impact we seeded edited HSPCs in methylcellulose and 14 days later harvested either bulk or individual colonies to analyse DNA methylation and/or genetic editing using targeted sequencing, gene expression using q-PCR and RNA-sequencing, and genome-wide DNA methylation analysis using the Illumina 850K array. We also engrafted the CRISPR/Cas9 edited human cells into NSG mice to check the repopulating capabilities of these cells. Results: Starting from as few as 50,000 cells using the CRISPR/Cas9 system we demonstrate dual epigenetic and genetic editing in the same CD34+ cell with DNA methylation targeted at p15 and p14 as well as mutating TET2. We find that despite using a transient delivery system, DNA methylation is maintained with some CpGs in myeloid colonies having up to 99% DNA methylation, and this results in inhibition of gene expression. We further show that HSCs with CRISPR targeted hypermethylation at p15 can repopulate the bone marrow of NSG mice and that p15 hypermethylation is maintained in vivo. Summary/Conclusion: We have demonstrated the feasibility of combining epigenetic and genetic editing in HSPCs, to recapitulate disease-relevant hits using CRISPR/dCas9 to help us study the cellular processes that may underlie myeloid cancer development.
P1585: THE ROLE OF INTESTINAL MICROBIOME IN SYSTEMIC INFECTIONS IN PATIENTS WITH MULTIPLE MYELOMA
Authors: V. Burylev, I. Kostroma, E. Kiseleva, N. Stizhak, E. Kaytandzhan, S. Gritsaev, S. Bessmeltsev, V. Chebotkevich
Journal: HemaSphere (2022)

Background: Intensive cytostatic therapy, used in the treatment of hemoblastosis, as well as conditioning therapy before hematopoietic stem cell transplantation (HSCT) lead to severe intestinal epithelial disorders, and massive antibacterial therapy leads to profound changes in the composition of the intestinal microbiome. Aims: to study the intestinal microbiome during cytostatic therapy and HSCT in patients with hemoblastosis and their role as predictors of the development of systemic bloodstream infections Methods: We studied the intestinal microbiome of 18 adult patients (8 women, 10 men, aged 54-66 years) with multiple myeloma (n=15) and nonHodgkin’s lymphoma (n=3), who underwent autoHSCT. From each patient we obtained the stool speciments before and after HSCT. Among the eligibility criteria for the study was accepted the presence of ≥ 3 consecutive high quality fecal specimens in the one patient. From each fecal specimen, DNA was extracted and purified and was sequenced using the MiSeq Illumina platform. The species diversity of the microbiome was assessed using the Shannon index. The index of microbial diversity (Shannon index) was calculated in different periods before and after autoHSCT. The significance of the differences was determined using the paired Student’s test. Results: A significant (p = 0.0305) decrease in the microbiota diversity index was revealed in the period after autoHSCT. . The characteristics of changes in the composition of the microbiome at the Phylum level before and after autoHSCT were studied. It was found that a significant change in the microbiome at the Phylum level was revealed only in relation to the Actinobacteria group. No significant changes in the level of Bacteroides, Firmicutes, and Proteobacteria were found. In this group of patients the bloodstream infection was determined in one case. During the observation in post transplant period we reveled the increase of E. coli in his stool specimen from 107 up to 109 which was regarded as a predictor of the development of a systemic infection of the bloodstream. Earlier we demonstrated the domination of E. coli in gram-negative systemic infections in immunocompromised oncohematological patients. [Chebotkevich V.N et al., Cellular Therapy and Transplantation. 2021. Т. 10. № 1. С. 63-68]. Summary/Conclusion: The study of the microbiome by sequencing using the MiSeq Illumina platform made it possible to identify important patterns of changes in the microbiota in oncohematological patients with autoHSCT. The most severe bloodstream infections in patients with hemoblastosis are associated with gram-negative microbes, of which E. coli is dominated.
Perinatal Depression and Beyond—Implications for Research Design and Clinical Management
Authors: Susan Garthus-Niegel, Sandra Nakić Radoš, Antje Horsch
Journal: JAMA Network Open (2022)

Pervez Sultan, MBChB; Kazuo Ando; Rania Elkhateb; Ronald B. George, MD; Grace Lim; Brendan Carvalho, MBBCh; Ahish Chitneni, MD; Ray Kawai; Tanya Tulipan, MD; Lindsay Blake, MLIS; Jessica Coker, MD; James O'Carroll, MBBS
Economic costs of dementia in 11 countries in Europe: Estimates from nationally representative cohorts of a panel study
Authors: Erik Meijer, Maria Casanova, Hyewon Kim, Ana Llena-Nozal, Jinkook Lee
Journal: The Lancet Regional Health - Europe (2022)

With population aging, the economic burden of dementia is growing in Europe. Understanding the economic costs of dementia provides an important basis for prioritization in public health policy and resource allocation.We calculate the economic costs of dementia, including both direct medical and social care costs and indirect costs of informal care, for 11 countries in Europe. Costs are estimated using population-representative data from the Survey of Health, Ageing, and Retirement in Europe from 2004 to 2017, supplemented with external information about wages of care workers, dementia prevalence, and fraction of direct costs paid by other sources. We report overall costs for persons, both living and deceased with dementia and also isolate the costs attributable to dementia by estimating regression models that relate a given cost component to dementia while controlling for coexisting conditions and demographics. We make the monetary data comparable by adjusting for inflation and Purchasing Power Parity to 2018 euros.Average annual direct out of pocket costs that can be attributed to dementia vary between EUR 253(95% CI: -17 to 522) and EUR 859 (95% CI: -587 to 2306) across countries, but are not statistically significant after adjustment for multiple testing. Average annual hours of informal care that can be attributed to dementia vary between 163 (95% CI: 27-299) and 1051 (95% CI: 15-2086) annual hours across countries, and are statistically significant in all countries before adjustment for multiple testing, and in seven out of 11 countries after this adjustment. Combining these estimates with external wage information in each country implies a burden between EUR 2687.4 (95% CI: 704.5 to 4670.3) and EUR 15,468 (95% CI: 8088.1 to 22,847.9) per individual with dementia per year depending on the country. When combined with external estimates of the fraction of direct costs covered by other payment sources (insurance, government) and numbers of individuals with dementia, estimates of the total costs of dementia at the country level vary from EUR 162.9 million (95% CI: 56.3 to 269.5) in Estonia to EUR 32,606.9 (95% CI: 13,893.9 to 51,319.9) in Germany. Informal care costs account for the largest proportion of costs attributable to dementia in all European countries, varying between about 50% and about 90%.The economic burden of dementia on families in terms of direct out-of-pocket and informal care costs varies greatly by country, depending on the health and social care systems. Informal care costs accounts for the largest proportion of costs, requiring policy attention to dementia care provision and costs.This project is funded by the National Institute on Aging, National Institutes of Health, USA (R01 AG030153).